Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA392929 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Gene expression and copy number variation arrays for parental GTL16 and GTL16 clones resistant to c-Met inhibitor.
2012-06-22 | GSE27692 | GEO
Project description:Gene expression and copy number variation arrays for parental GTL16 and GTL16 clones resistant to c-Met inhibitor. Affymetrix U133 Plus 2.0 and SNP 6.0 chips were used to assess gene expression and copy number variation, respectively, of GTL16 and resistant GTL16 clones.
2012-06-21 | E-GEOD-27692 | biostudies-arrayexpress
Project description:Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase is overexpressed in 90% of Head and neck squamous cell carcinoma (HNSCC) patients. Clinical trials with EGFR-targeted tyrosine kinase inhibitors such as erlotinib have shown a modest activity in HNSCC alternate mechanisms of resistance are acquired. To investigate these acquired mechanisms of resistance and identify novel therapeutic targets we employed whole exome sequencing of an isogenic pair of erlotinib sensitive (SCC-S) and resistant (SCC-R) HNSCC cell line. We observed single nucleotide variations and copy number alterations in genes related to RAS-RAF-MEK-ERK pathway. To assess the effects of these variations on cellular kinome and we employed SILAC-based phosphoproteomic analysis of SCC-S and SCC-R cell lines. Quantitative phosphoprotein profiling led to identification of 5558 unique phosphopeptides and 5025 unique phosphosites corresponding to 2344 proteins. We observed, 903 phosphopeptides belonging to 579 proteins and 518 phosphopeptides belonging to 368 proteins to be hyper and hypophosphorylated (≥2 fold) in SCC-R cells, respectively. Bioinformatics analysis of differentially phosphorylated proteins showed enrichment of proteins involved in MAPK pathway downstream of EGFR. We identified and validated activation of proteins related to MAPK pathway and its downstream targets in SCC-R cells. We further demonstrated that MAP2K1 inhibitor can be used as an alternative to erlotinib in HNSCC.
2019-12-18 | PXD007785 | Pride
Project description:Copy number profiling of MKN45T 5-FU resistant gastric cancer cell lines and its parental cell line MKN45. We hypothesized that a detailed fine-scale survey of genomic CNAs might reveal the mechanism for acquired resistant to 5-FU in gastric cancer.
2017-06-09 | GSE89191 | GEO
Project description:To compare gene copy number in cell populations with acquired resistance to specified EGFR inhibitors to parental cell lines. The aim of the experiment was to determine whether gain or loss of copy number of particular genes was associated with resistance to particular EGFR inhibitors. Comparing gene copy number in PC9 parental cells to gene copy number in 5 cell populations resistant to AZD9291, 2 cell populations resistant to WZ4002, 2 cell populations resistant to afatinib and 4 cell populations resistant to gefitinib.
2015-04-14 | E-GEOD-59239 | biostudies-arrayexpress
Project description:Copy number analysis to compare parental colorectal cancer cell lines and their selumetinib-resistant derivatives and identify gene copy changes that might contribute to resistance
2019-03-11 | GSE126367 | GEO
Project description:Bortezomib is a proteasome inhibitor used in severel different hematological malignancies. Resistance to this drug is still poorly understood. In order get more insight in the resistance mechanism, we developed several bortezomib resistant subclones of the CCRF-CEM T-ALL cell line. On these subclones comparative Genome hybridization (arrayCGH) for DNA copy number analysis gene expression and micro-RNA expression arrays were performed. We performed comparative Genome hybridization (arrayCGH) for DNA copy number analysis on four different bortezomib resistant subclones of the CCRF-CEM cell line. The resistant subclones were compared to the parental CCRF-CEM wildtype cell line and reference DNA.
2015-11-04 | E-GEOD-74633 | biostudies-arrayexpress
Project description:The clinical efficacy of EGFR kinase inhibitors is limited by the development of drug resistance. The irreversible EGFR kinase inhibitor WZ4002 is effective against the most common mechanism of drug resistance mediated by the EGFR T790M mutation. Here we show that in multiple complementary models harboring EGFR T790M, resistance to WZ4002 develops through aberrant activation of ERK signaling caused by either an amplification of MAPK1 or by downregulation of negative regulators of ERK signaling. Inhibition of MEK or ERK restores sensitivity to WZ4002, and the combination of WZ4002 and a MEK inhibitor prevents the emergence of drug resistance. The WZ4002 resistant MAPK1 amplified cells also demonstrate an increase both in EGFR internalization and a decrease in sensitivity to cytotoxic chemotherapy compared to the parental counterparts. Our findings provide insights into mechanisms of drug resistance to EGFR kinase inhibitors and highlight rational combination therapies that should be evaluated in clinical trials. The EGFR mutant non-small cell lung cancer (NSCLC) cell line PC9 GR4 (delE746_A750/T790M) was exposed to increasing concentrations of WZ4002 similar to previously described methods. Individual clones from WZ4002-resistant (WZR) cells were isolated and confirmed to be drug resistant. Number of samples: 5. PC9GR4 as a control. 4 clones of WZ4002-resistant PC9GR4.
2012-10-01 | E-GEOD-37698 | biostudies-arrayexpress
Project description:Bortezomib is a proteasome inhibitor used in severel different hematological malignancies. Resistance to this drug is still poorly understood. In order get more insight in the resistance mechanism, we developed several bortezomib resistant subclones of the CCRF-CEM T-ALL cell line. On these subclones comparative Genome hybridization (arrayCGH) for DNA copy number analysis gene expression and micro-RNA expression arrays were performed. We performed micro-RNA on two different bortezomib resistant subclones of the CCRF-CEM cell line. The resistant subclones were compared to the parental CCRF-CEM wildtype cell line.
2015-11-04 | E-GEOD-74632 | biostudies-arrayexpress
Project description:The clinical efficacy of EGFR kinase inhibitors is limited by the development of drug resistance. The irreversible EGFR kinase inhibitor WZ4002 is effective against the most common mechanism of drug resistance mediated by the EGFR T790M mutation. Here we show that in multiple complementary models harboring EGFR T790M, resistance to WZ4002 develops through aberrant activation of ERK signaling caused by either an amplification of MAPK1 or by downregulation of negative regulators of ERK signaling. Inhibition of MEK or ERK restores sensitivity to WZ4002, and the combination of WZ4002 and a MEK inhibitor prevents the emergence of drug resistance. The WZ4002 resistant MAPK1 amplified cells also demonstrate an increase both in EGFR internalization and a decrease in sensitivity to cytotoxic chemotherapy compared to the parental counterparts. Our findings provide insights into mechanisms of drug resistance to EGFR kinase inhibitors and highlight rational combination therapies that should be evaluated in clinical trials. Our study identifies ERK signaling as a mediator of resistance to irreversible pyrimidine EGFR inhibitors in EGFR T790M-bearing cancers. We further provide a therapeutic strategy to both treat and prevent the emergence of this resistance mechanism. To generate drug-resistant NCI-H1975 cell lines, non-small cell lung cancer (NSCLC) cells were exposed to increasing concentrations of WZ4002 similar to previously described methods. Individual clones from WZ4002-resistant (WZR) cells were isolated and confirmed to be drug resistant. Clone #6, designated as WZR6, was used in this study. For expression analysis, samples were prepared in triplicate from parental NCI-H1975 and NCI-H1975 WZR6 cells.
2012-10-01 | E-GEOD-37699 | biostudies-arrayexpress